Metformin Should Be Used to Treat Prediabetes in Selected Individuals

Abstract

In this issue of Diabetes Care , Dr. Mayer Davidson proposes that prescription of metformin for patients with prediabetes is inappropriate (1). We respectfully disagree. Hyperglycemia is a continuous risk factor for adverse health outcomes. Both the degree and duration of hyperglycemia are associated with the development and progression of diabetic microvascular and macrovascular complications (2), and early aggressive management of hyperglycemia in both type 1 and type 2 diabetes confers lifelong health benefits (3,4). We believe that Dr. Davidson’s approach to watchful waiting, “to follow [high-risk individuals] closely and immediately introduce metformin when their glycemia meets the criteria for diabetes…,” is inadequate. Numerous studies have demonstrated that there is a delay of 3–8 years between the onset and the diagnosis of type 2 diabetes (5), and at the time of diagnosis as many as 8–16% of patients have diabetic retinopathy, 17–22% have microalbuminuria, and 14–48% have peripheral polyneuropathy (6,7). A recent epidemiologic analysis of new-onset diabetes in the U.K. demonstrated a statistically significant increased risk of microvascular complications at diagnosis among individuals identified previously with prediabetes compared with those with previous normal glucose tolerance (adjusted odds ratio of 1.76 for retinopathy and 1.14 for nephropathy) (8). Therefore, there is no reason to withhold metformin, a safe, effective, and cost-saving treatment to delay or prevent the development of type 2 diabetes, from individuals at high risk. That said, a number of caveats apply. First, the Diabetes Prevention Program (DPP) and indeed most of the other major diabetes prevention trials studied individuals at extremely …